Baseline erythrocyte sedimentation rate level predicts long-term inhibition of radiographic progression by tocilizumab: the KURAMA cohort

Figures & data

Figure 1. Cumulative probability plots of radiographic progression assessed by the modified Total Sharp Score (mTSS, U/year). Thirty-four patients (57.6%) showed structural remission (ΔmTSS/year ≤0.5), whereas 7 patients showed clinically relevant radiographic progression (ΔmTSS/year >3).

Figure 2. Cumulative probability plots of radiographic progression assessed by the modified Total Sharp Score (mTSS, U/year) sorted by clinical parameters. (A) Sorted by rheumatoid factor (RF) positivity. (B) Sorted by methotrexate (MTX) use. (C) Sorted by prednisolone (PSL) use. (D) Sorted by anti-cyclic citrullinated peptide antibodies (ACPA) positivity. The structural remission rate (ΔmTSS/year ≤0.5) was not affected by RF positivity (p = 1.0), concomitant use of MTX (p = .79), concomitant use of PSL (p = .59), but ACPA-positive patients tended to show higher structural remission rate than ACPA-negative patients (p = .08).

Table 1. Comparison between patients who achieved structural remission and those who did not.

	Not achieved	Achieved	p value
Patients (n)	25	34
Age (year, median, IQR)	64 [58–68]	59 [51–65]	.06
Female (n, %)	23 (92.0%)	25 (73.5%)	.10
Disease duration (year, median, IQR)	6.5 [3.0–17.0]	7.0 [2.5–16.0]	.73
RF-positive (n, %)	16 (72.7%)	26 (76.5%)	.76
ACPA-positive (n, %)	18 (72.0%)	31 (91.2%)	.08
Duration of TCZ administration (year, median, IQR)	3.1 [2.9–3.6]	3.1 [2.9–3.4]	.7
Concomitant MTX at TCZ introduction (mg/w, median, IQR)	8.0 [6.0–10.0]	10.0 [6.0–12.0]	.24
Concomitant PSL at TCZ introduction (mg/d, median, IQR)	5.0 [4.0–7.0]	5.0 [5.0–7.5]	.49
History of b/tsDMARDs (n, %)	17 (68%)	27 (79.4%)	.72
TCZ as a 1st bDMARD	8 (32.0%)	7 (20.6%)	.37
TCZ as a 2nd bDMARD	6 (24.0%)	11 (32.4%)	.57
TCZ as a 3rd bDMARD	7 (28.0%)	8 (23.5%)	.77
TCZ as a 4th or later bDMARD	4 (16.0%)	8 (23.5%)	.53
ESR at TCZ introduction (mm/h, median, IQR)	65.5 [38.5–88.5]	28.0 [19.0–54.0]	.003
CRP at TCZ introduction (mg/dL, median, IQR)	2.2 [0.65–5.5]	0.6 [0.18–2.9]	.05
Difficult-to-treat RA at TCZ introduction (n, %)	3 (12%)	4 (11.8%)	1.0
CDAI at TCZ introduction (median, IQR)	12.5 [6.0–19.3]	14.3 [10.2–17.0]	.84
CDAI at 12 months (median, IQR)	2.7 [1.5–5.4]	3.1 [1.0–8.6]	.98
CDAI at 24 months (median, IQR)	3.3 [1.4–7.0]	3.3 [0.6–7.16]	.79
Total IgG (mg/dL, median, IQR)	1489 [1207–1627]	1468 [1099–1720]	.78

p-values were calculated to compare the clinical characteristics of patients who showed structural remission with those of patients who did not. Mann–Whitney U test for continuous variables and Fisher’s exact test for categorical variables. ACPA: anti-cyclic citrullinated peptide antibodies; b/tsDMARDs: biological or targeted synthetic disease-modifying anti-rheumatic drugs; CDAI: clinical disease activity index; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; IQR: interquartile range; MTX: methotrexate; PSL: prednisolone; RA: rheumatoid arthritis; RF: rheumatoid factor; TCZ: tocilizumab.

Table 2. Multivariate logistic analysis for long-term structural remission by tocilizumab.

	Model 1				Model 2
	Odds ratio	95%CI lower	95%CI upper	p value		Odds ratio	95%CI lower	95%CI upper	p value
Age	0.96	0.90	1.0	.33	Age	0.975	0.90	1.03	.32
Female	1.93	0.31	12.2	.48	Female	2.45	0.42	14.5	.32
ACPA-positive	6.5	1.18	36	.032	ACPA (U/mL)	1	0.99	1	.60
ESR (mm/h)	0.97	0.95	0.99	.032	ESR (mm/h)	0.98	0.96	0.99	.049

Multivariate logistic regression analysis. ACPA: anti-cyclic citrullinated peptide antibody; CI: confidence interval; ESR: erythrocyte sedimentation rate.

Figure 3. Baseline erythrocyte sedimentation rate (ESR) predicts long-term structural remission by tocilizumab. (A) Receiver operating characteristics (ROC) analysis was performed to determine the cutoff value of baseline ESR. The cutoff value of baseline ESR was determined to be 73 mm/h (area under the curve [AUC]: 0.71, 95%CI: 0.56–0.86, p = .008). (B) The structural remission rate was significantly higher in patients with baseline ESR level <73 mm/h than that in those with a baseline ESR level of ≥73 mm/h (p = .006). Annual progression of erosion (C) and joint space narrowing (D) were both reduced in the lower ESR group than in the higher ESR group (p = .0036, p = .0021, respectively). The data are presented as mean + SD.